Viking Therapeutics has announced the initiation of the SUNRISE phase 3 clinical program for oral VK2735, the company's dual agonist of the Glucagon-Like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) receptors. VK2375 is being developed in both oral and subcutaneous formulations for the potential treatment of various metabolic disorders such as obesity.

The SUNRISE phase 3 program includes 2 studies evaluating oral VK2735: one in adults with obesity and another in obese or overweight adults with Type 2 Diabetes (T2D). Each study is a randomised, double-blind, placebo-controlled, multicenter trial designed to assess the efficacy and safety of VK2735, with patients receiving once-daily oral VK2735 for 68 weeks.

SUNRISE-1 and SUNRISE-2 will each target enrolment of 560 adults. SUNRISE-1 will include obese (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) adults without T2D who have at least one weight-related comorbidity. SUNRISE-2 will enroll adults with T2D who are obese or overweight. Participants in both trials will be randomly assigned to 1 of 4 treatment groups receiving once-daily VK2735 doses of 27.5 mg, 35 mg, 55 mg, or placebo.

The primary endpoint of both trials is the percent change in body weight from baseline for participants receiving oral VK2735 as compared to placebo after 68 weeks of treatment. Secondary and exploratory endpoints will evaluate a range of additional safety and efficacy metrics, including the percentage of patients who achieve ≥ 5 percent, ≥ 10 percent, ≥ 15 percent or ≥ 20 percent body weight reduction from baseline. 

Brian Lian, PhD, Chief Executive Officer, Viking Therapeutics, said, "Advancing the oral tablet formulation of VK2735 into phase 3 is an exciting step toward expanding Viking's portfolio of therapeutic treatments for obesity. Oral VK2735 represents the most advanced oral dual GLP-1/GIP agonist in clinical development and has the potential to be positioned as either an induction therapy or in the maintenance setting, increasing the treatment options available to patients and clinicians. Obesity is a chronic disease that often requires long-term treatment, making convenience and ease of use important considerations for supporting patients throughout their treatment journey. We believe a once-daily oral therapy could offer a flexible dosing option that may support improved treatment adherence over time. Oral VK2735, together with our subcutaneous formulation, which is currently in the phase 3 VANQUISH registration program, could provide clinicians and patients with greater choice in selecting an approach to weight loss and long-term management that best meets the needs of individual patients."

In 2025, Viking announced positive top-line results from the phase 2 VENTURE-Oral Dosing study of the oral tablet formulation of VK2735 in obesity. The study successfully achieved its primary and secondary endpoints, with patients receiving once-daily oral VK2735 demonstrating clinically meaningful reductions in body weight compared with placebo.

For the primary endpoint after 13 weeks of treatment, patients receiving oral VK2735 demonstrated statistically significant, dose-dependent reductions in mean body weight from baseline of up to 12.2 percent.

Differences compared with placebo were statistically significant for all doses greater than 15 mg starting at week 1 and were maintained throughout the study. Weight loss was progressive through week 13 with no evidence of a plateau. Up to 97 percent of patients receiving oral VK2735 achieved at least 5 percent weight loss, and up to 80 percent achieved at least 10 percent weight loss, compared with 10 percent and 5 percent of patients receiving placebo, respectively.

Oral VK2735 also demonstrated encouraging safety and tolerability in the phase 2 VENTURE-Oral study, with 98 percent of reported drug-related Treatment-Emergent Adverse Events (TEAEs) characterised as mild or moderate.

Gastrointestinal (GI)-related events were the most commonly observed TEAEs and were consistent with the known effects of dual GLP-1/GIP receptor agonists. Across VK2735 treatment cohorts, GI-related events generally occurred early in treatment and subsided with continued dosing. Progressive dose escalation in 30 mg increments enabled participants to advance rapidly to higher dose levels while maintaining an encouraging tolerability profile.

In addition to the SUNRISE phase 3 program, Viking is currently conducting a maintenance dosing trial of oral VK2735 and 2 phase 3 studies evaluating subcutaneous VK2735 (VANQUISH-1 and VANQUISH-2).

The VANQUISH trials are randomised, double-blind, placebo-controlled, multicenter trials designed to assess the efficacy and safety of subcutaneous VK2735 dosed weekly for 78 weeks.

The VANQUISH-1 study is fully enrolled with approximately 4,500 adults who do not have T2D and who have obesity (BMI ≥30 kg/m²) or are overweight (BMI ≥27 kg/m²) with at least one weight-related co-morbid condition.

The VANQUISH-2 study is also fully enrolled with approximately 1,000 adults with T2D who have obesity or are overweight.

Patients in both trials are being randomised to 1 of 4 weekly VK2735 treatment arms of 7.5 mg, 12.5 mg, 17.5 mg, or placebo.